DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-88 were originally filed June 6, 2023.
The amendment received June 9, 2023 amended claims 2, 7-11, 13, 14, 23, 24, 26, 35, 40, 43, 48, 49, and 78 and canceled claims 3, 12, 15-22, 27-34, 36-39, 41, 42, 50-71, 73-77, and 79-88.
The amendment received October 27, 2023 amended clams 2, 7-11, 13, 14, 23, 24, 26, 35, 40, 43, 48, 49, and 78 and canceled claims 4-6 and 44-47.
The amendment received January 26, 2026 amended claims 10, 26, and 78; canceled claims 25, 35-42, 48, and 72; and added new claims 89-93.
Claims 1, 2, 7-11, 13, 14, 23, 24, 26, 43, 49, 78, and 89-93 are currently pending.
Claims 1, 2, 7, 8, 10, 11, 13, 14, 23, and 89-93 are currently under examination.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1, 2, 7-11, 13, 14, 23, and 24; new claims 89-93) in the reply filed on January 26, 2026 is acknowledged.
Claims 26, 43, 49, and 78 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected products and methods, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 26, 2026.
Applicant’s election without traverse of SEQ ID NO: 5, PBS, BSA, and CRM197 as the species in the reply filed on January 26, 2026 is acknowledged.
Please note: elections of subgenuses (i.e. saline, formulation as a solution comprising a carrier protein, the solution further comprises a carrier protein that increases delivery across the BBB) are considered nonresponsive. In addition, the election of species is not optional (i.e. “for example”). The election of species should be definitive.
Please note: SEQ ID NO: 5 is known in the art as secretoneurin which is a cleavage product of present SEQ ID NO: 4 (i.e. residues 182-214 of human precursor SCG2; see paragraphs 125 and 140 of the present specification).
Claim 24 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 26, 2026.
Please note: claims 10, 11, and 13 should be withdrawn due to the election of SEQ ID NO: 5. However, due to issues with the claims, the claims have been examined. This does not preclude the withdrawal of the claims at a later date or a new species requirement.
Potential Rejoinder
Applicant elected claims directed to a product. If a product claim is subsequently found allowable, withdrawn process claims that depend from or otherwise include all the limitations of the allowable product claim will be rejoined in accordance with the provisions of MPEP § 821.04. Process claims that depend from or otherwise include all the limitations of the patentable product will be entered as a matter of right if the amendment is presented prior to final rejection or allowance, whichever is earlier. Amendments submitted after final rejection are governed by 37 CFR 1.116; amendments submitted after allowance are governed by 37 CFR 1.312.
In the event of rejoinder, the requirement for restriction between the product claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all the criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103, and 112. Until an elected product claim is found allowable, an otherwise proper restriction requirement between product claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowed product claim will not be rejoined. See “Guidance on Treatment of Product and Process Claims in light of In re Ochiai, In re Brouwer and 35 U.S.C. § 103(b),” 1184 O.G. 86 (March 26, 1996). Additionally, in order to retain the right to rejoinder in accordance with the above policy, applicant is advised that the process claims should be amended during prosecution either to maintain dependency on the product claims or to otherwise include the limitations of the product claims. Failure to do so may result in a loss of the right to a rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Priority
The present application is a 371 (National Stage) of PCT/US2021/061950 filed December 6, 2021 which claims the benefit of 63/122,156 filed December 7, 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on June 6, 2023 and January 8, 2025 are being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
See Figure 4F.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See paragraphs 295 and 468.
The disclosure is objected to because of the following informalities: the nucleic acids in paragraphs 40-43, 184-187, and 438 and pages 105 and 106 should be in lower case.
Appropriate correction is required. See MPEP § 2422.
The disclosure is objected to because of the following informalities: the amino acids in Table 3 (SEQ ID NOs: 45, 50, 52, 64, and 67) and in paragraphs 208 and 298-300 should be in upper case. See MPEP § 2422.
Appropriate correction is required.
Claim Objections
Claim 7 is objected to because of the following informalities: a single conjunction of “and” should be present in the Markush group (see line 7 – missing conjunction). Appropriate correction is required.
Claim 7 is objected to because of the following informalities: “or” should be removed form lines 3, 5, 6, and 7. Appropriate correction is required.
Claim 7 is objected to because of the following informalities: non-elected subject matter is present in the claim (i.e. formulation as a nucleic acid – see line 4 and formulation as a CNS-tropic viral vector – see line 5). It is also respectfully note that “nucleic acid” is a single nucleic acid and not a polynucleotide. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: “of secretogranin II (scg2) polypeptide” should read “of a scg2 polypeptide”. Appropriate correction is required.
Claim 10 is objected to because of the following informalities: personalization of inanimate objects is not typical of scientific writing (i.e. its – see lines 2 and 3). Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear what is required by the claim to be formulated for delivery to the CNS, across the BBB, to the brain, and/or to pyramidal cells (e.g. special carrier, fusion to something, etc.).
Claim 7 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. One of skill in the art would not be able to determine the scope of the present claims. For example, a member of the Markush group is drawn to intended use (i.e. direct injection or infusion into the CNS). Therefore, it is unclear what is required by the claim.
Claim 7 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear how “formulation with or linkage to an agent that is endogenously transported across the BBB”, “formulation with or linkage to a BBB-shuttle”, and “formulation with or linkage to an agent that increases permeability of the BBB” differ (e.g. different members of the Markush group should require different structures).
Claim 7 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear what “with” and “linkage” require. The composition, solution, formulations, etc. should be clarified (e.g. non-covalent linkage, covalent linkage, in solution, etc.).
Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear how the SCG2 neuropeptide can be a cleavage product of a SCG2 polypeptide (i.e. how does the structure of the SCG2 neuropeptide and the SCG2 polypeptide differ). Applicants should claim the broadest limitation (e.g. SCG2 polypeptide, SCG2 polypeptide and fragments thereof, SCG2 polypeptide and cleavage products thereof, etc.) in the independent claim and then narrow the limitations of the dependent claims.
Claim 10 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear if the dibasic cleavage residues are required by the claim or not. Since claim 8 from which claim 10 depends is drawn to the cleavage product, it is presumed that at least part, if not all, of the dibasic cleavage residue would be cleaved (i.e. not part of the SCG2 neuropeptide).
Claim 11 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear if the dibasic cleavage residues are required by the claim or not. Since claim 8 from which claim 11 indirectly depends is drawn to the cleavage product, it is presumed that at least part, if not all, of the dibasic cleavage residues would be cleaved (i.e. not part of the SCG2 neuropeptide).
Claim 13 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear if the dibasic cleavage residue is required by the claim or not. Since claim 8 from which claim 13 indirectly depends is drawn to the cleavage product, it is presumed that at least part, if not all, of the dibasic cleavage residues would be cleaved (i.e. not part of the SCG2 neuropeptide).
Claim 14 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear if the SCG2 peptide is closed or open. This is due to the inclusion of both closed (i.e. selected from the group consisting of) and open (i.e. comprising – see “a)”, “b)”, “c)”, and “d)”) claim language. See the sequence interpretation section below.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 2 is dependent on independent claim 1. Independent claim 1 requires a SCG2 and a pharmaceutically acceptable carrier. Dependent claim 2 refers to formulations with specific attributes, but does not provide any structure to correlate to the attributes. Therefore, the pharmaceutically acceptable carrier could provide the attributes as claimed. Dependent claim 2 fails to alter the structure and/or the composition of the pharmaceutical composition of claim 1 (i.e. failure to further limit). Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 7 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 7 is dependent on independent claim 1. Independent claim 1 requires a SCG2 and a pharmaceutically acceptable carrier. Dependent claim 7 refers to an intended use (i.e. direct injection or infusion into the CNS). The pharmaceutically acceptable carrier could provide the solution. Dependent claim 7 (one member of the Markush group) fails to alter the structure and/or the composition of the pharmaceutical composition of claim 1 (i.e. failure to further limit). Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 8 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 8 depends on independent claim 1. Independent claim requires a SCG2 neuropeptide. Dependent claim 8 requires the SCG2 neuropeptide to be a cleavage product of a SCG2 polypeptide. Therefore, it appears that dependent claim 8 may fail to further limit the scope of independent claim 1 (e.g. independent claim 1 should recite the broadest limitation and dependent claim 8 should narrow the limitation of independent claim 1). Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 10 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 10 depends on claim 8. Claim 8 requires a cleavage product of a SCG2 polypeptide. Claim 10 refers to a dibasic cleavage residue. It is assumed that since claim 8 requires the cleavage product that part, if not all, of the dibasic cleavage residue is cleaved (i.e. not part of the SCG2 neuropeptide). Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 11 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 11 depends on claim 10. Claim 10 depends on claim 8. Claim 8 requires a cleavage product of a SCG2 polypeptide. Claim 11 refers to dibasic cleavage residues of RK, KR, or RR. It is assumed that since claim 8 requires the cleavage product that part, if not all, of the dibasic cleavage residue is cleaved (i.e. not part of the SCG2 neuropeptide). Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 13 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 13 depends on claim 10. Claim 10 depends on claim 8. Claim 8 requires a cleavage product of a SCG2 polypeptide. Claim 13 refers to a dibasic cleavage residue specific for Pcsk1/2 protease. It is assumed that since claim 8 requires the cleavage product that part, if not all, of the dibasic cleavage residue is cleaved (i.e. not part of the SCG2 neuropeptide). Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Improper Markush
Claim 7 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of claim 7 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the Markush grouping do not share a single structural similarity (e.g. solution, carrier protein, nanoparticle, liposome, nucleic acid, viral vector, agent that crosses BBB, CPP, BBB-shuttle, agent that increases permeability of the BBB) or a common use (e.g. solution for holding SCG2, nanoparticle with SCG2, liposome with SCG2, polynucleotide presumably encoding SCG2, viral vector presumably for the expression of SCG2, CPP to transport into a cell, transport across BBB).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Please note: due to the myriad of objections and 35 USC 112 issues with the claims, applicants are respectfully requested to carefully review the claims for any additional issues.
Sequence Interpretation
The Office interprets claims comprising SEQ ID NOs: in the following manner: “comprising a sequence of SEQ ID NO: 1” requires only a 2mer of SEQ ID NO: 1, “comprising the sequence of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 with any N-/C-terminal additions or any 5’/3’ additions, “consisting of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 and the same length as SEQ ID NO: 1, and “selected from the group consisting of SEQ ID NOs: 1, 2, and 3” requires the full-length sequence with 100% identity to SEQ ID NOs: 1, 2, or 3 and the same length as SEQ ID NOs: 1, 2, or 3. Any claim requiring a specific percent identity, necessarily requires at least the recited percent identity.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 2, 7-11, 13, 14, 23, and 89-93 rejected under 35 U.S.C. 101 because the claimed invention is directed to SCG2 (SEQ ID NO: 4 - claim 9; human, mouse, rat, or chimpanzee – claim 23), SCG2 naturally occurring fragments (SEQ ID NO: 5; claim 14), and SCG2 fragments (claims 8-11, 13, 14) without significantly more. The claims recite at least one SCG2 neuropeptide and a pharmaceutically acceptable carrier. Dependent claim 7 also refers to solutions, nanoparticles, liposomes, polynucleotide, agents to cross the BBB, and CPP wherein the formulation is “with” or has a “linkage”. Dependent claims 89-93 refer to saline, PBS, BSA, and CRM197. This judicial exception is not integrated into a practical application because the present claims are drawn to a product. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because it is unclear how the additional components are associated with the SCG2 neuropeptide (e.g. “with” and “linkage are not defined” and formulation is unclear with regard to the association with SCG2). In addition, carriers, protein carriers, solutions, nanoparticles, liposomes, agents that cross the BBB, CPP, saline, PBS, BSA, and CRM197 are well-understood, routine, and conventional in the prior art.
SEQ ID NO: 5
RESULT 1
Q2ERU2_FELCA
ID Q2ERU2_FELCA Unreviewed; 114 AA.
AC Q2ERU2;
DT 21-MAR-2006, integrated into UniProtKB/TrEMBL.
DT 21-MAR-2006, sequence version 1.
DT 08-OCT-2025, entry version 36.
DE RecName: Full=Secretogranin-2 {ECO:0000256|ARBA:ARBA00013649};
DE AltName: Full=Secretogranin II {ECO:0000256|ARBA:ARBA00032429};
DE Flags: Fragment;
GN Name=SGII {ECO:0000313|EMBL:ABD24220.1};
OS Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685 {ECO:0000313|EMBL:ABD24220.1};
RN [1] {ECO:0000313|EMBL:ABD24220.1}
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Adrenal medulla {ECO:0000313|EMBL:ABD24220.1};
RX PubMed=16101435; DOI=10.2174/1389203054546334;
RA Fischer-Colbrie R., Kirchmair R., Kahler C.M., Wiedermann C.J., Saria A.;
RT "Secretoneurin: a new player in angiogenesis and chemotaxis linking nerves,
RT blood vessels and the immune system.";
RL Curr. Protein Pept. Sci. 6:373-385(2005).
RN [2] {ECO:0000313|EMBL:ABD24220.1}
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Adrenal medulla {ECO:0000313|EMBL:ABD24220.1};
RA Fischer-Colbrie R., Reinalter H.;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Neuroendocrine protein of the granin family that regulates
CC the biogenesis of secretory granules. {ECO:0000256|ARBA:ARBA00003092}.
CC -!- SUBUNIT: Interacts with Secretogranin III/SCG3.
CC {ECO:0000256|ARBA:ARBA00011376}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000256|ARBA:ARBA00004613}.
CC -!- SIMILARITY: Belongs to the chromogranin/secretogranin protein family.
CC {ECO:0000256|ARBA:ARBA00005723}.
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DR EMBL; DQ366896; ABD24220.1; -; mRNA.
DR AlphaFoldDB; Q2ERU2; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030141; C:secretory granule; IEA:InterPro.
DR InterPro; IPR001990; Granin.
DR InterPro; IPR038858; ScgII.
DR PANTHER; PTHR15119; SECRETOGRANIN II; 1.
DR PANTHER; PTHR15119:SF0; SECRETOGRANIN-2; 1.
DR Pfam; PF01271; Granin; 1.
PE 2: Evidence at transcript level;
KW Cleavage on pair of basic residues {ECO:0000256|ARBA:ARBA00022685};
KW Secreted {ECO:0000256|ARBA:ARBA00022525};
KW Signal {ECO:0000256|ARBA:ARBA00022729}.
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT NON_TER 1
FT /evidence="ECO:0000313|EMBL:ABD24220.1"
FT NON_TER 114
FT /evidence="ECO:0000313|EMBL:ABD24220.1"
SQ SEQUENCE 114 AA; 13571 MW; 264A8C26181C7FE8 CRC64;
Query Match 100.0%; Score 167; Length 114;
Best Local Similarity 100.0%;
Matches 33; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TNEIVEEQYTPQSLATLESVFQELGKLTGPNNQ 33
|||||||||||||||||||||||||||||||||
Db 59 TNEIVEEQYTPQSLATLESVFQELGKLTGPNNQ 91
SEQ ID NO: 4
RESULT 1
SCG2_HUMAN
ID SCG2_HUMAN Reviewed; 617 AA.
AC P13521; B2R662; Q53T11; Q8TBH3;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 18-JUN-2025, entry version 196.
DE RecName: Full=Secretogranin-2;
DE AltName: Full=Chromogranin-C;
DE AltName: Full=Secretogranin II;
DE Short=SgII;
DE Contains:
DE RecName: Full=Secretoneurin;
DE Short=SN;
DE Contains:
DE RecName: Full=Manserin;
DE Flags: Precursor;
GN Name=SCG2; Synonyms=CHGC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SULFATION AT TYR-151.
RC TISSUE=Pituitary;
RX PubMed=2745426; DOI=10.1016/s0021-9258(18)80167-3;
RA Gerdes H.-H., Rosa P., Phillips E., Baeuerle P.A., Frank R., Argos P.,
RA Huttner W.B.;
RT "The primary structure of human secretogranin II, a widespread tyrosine-
RT sulfated secretory granule protein that exhibits low pH- and calcium-
RT induced aggregation.";
RL J. Biol. Chem. 264:12009-12015(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Caudate nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLY-294; GLY-421 AND
RP GLY-535.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 182-214.
RX PubMed=9654353; DOI=10.1016/s0304-3940(98)00345-0;
RA Leitner B., Schneitler C., Klocker H., Volknandt W., Zimmermann H.,
RA Winkler H., Fischer-Colbrie R.;
RT "Formation and sequence analysis of secretoneurin, a neuropeptide derived
RT from secretogranin II, in mammalian, bird, reptile, amphibian and fish
RT brains.";
RL Neurosci. Lett. 248:105-108(1998).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pituitary;
RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x;
RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
RT "Phosphoproteomic analysis of the human pituitary.";
RL Pituitary 9:109-120(2006).
RN [8]
RP INTERACTION WITH SCG3, AND FUNCTION.
RX PubMed=19357184; DOI=10.1677/joe-08-0531;
RA Hotta K., Hosaka M., Tanabe A., Takeuchi T.;
RT "Secretogranin II binds to secretogranin III and forms secretory granules
RT with orexin, neuropeptide Y, and POMC.";
RL J. Endocrinol. 202:111-121(2009).
RN [9]
RP GLYCOSYLATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23234360; DOI=10.1021/pr300963h;
RA Halim A., Ruetschi U., Larson G., Nilsson J.;
RT "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT of human cerebrospinal fluid glycoproteins.";
RL J. Proteome Res. 12:573-584(2013).
CC -!- FUNCTION: Neuroendocrine protein of the granin family that regulates
CC the biogenesis of secretory granules. {ECO:0000269|PubMed:19357184}.
CC -!- SUBUNIT: Interacts with Secretogranin III/SCG3.
CC {ECO:0000269|PubMed:19357184}.
CC -!- INTERACTION:
CC P13521; Q8WXE1: ATRIP; NbExp=3; IntAct=EBI-947132, EBI-747353;
CC P13521; Q8WXD2: SCG3; NbExp=2; IntAct=EBI-947132, EBI-12162999;
CC P13521; Q9UMX0: UBQLN1; NbExp=4; IntAct=EBI-947132, EBI-741480;
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Neuroendocrine and endocrine
CC secretory granules.
CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:23234360}.
CC -!- MISCELLANEOUS: Binds calcium with a low-affinity.
CC -!- SIMILARITY: Belongs to the chromogranin/secretogranin protein family.
CC {ECO:0000305}.
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DR EMBL; M25756; AAA36607.1; -; mRNA.
DR EMBL; AK312452; BAG35359.1; -; mRNA.
DR EMBL; AC012512; AAY24243.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70811.1; -; Genomic_DNA.
DR EMBL; BC022509; AAH22509.1; -; mRNA.
DR CCDS; CCDS2457.1; -.
DR PIR; A34174; A34174.
DR RefSeq; NP_003460.2; NM_003469.5.
DR AlphaFoldDB; P13521; -.
DR SMR; P13521; -.
DR BioGRID; 113611; 17.
DR CORUM; P13521; -.
DR FunCoup; P13521; 174.
DR IntAct; P13521; 12.
DR MINT; P13521; -.
DR STRING; 9606.ENSP00000304133; -.
DR iPTMnet; P13521; -.
DR PhosphoSitePlus; P13521; -.
DR BioMuta; SCG2; -.
DR DMDM; 143811457; -.
DR jPOST; P13521; -.
DR MassIVE; P13521; -.
DR PaxDb; 9606-ENSP00000304133; -.
DR PeptideAtlas; P13521; -.
DR ProteomicsDB; 52923; -.
DR Antibodypedia; 2205; 339 antibodies from 33 providers.
DR DNASU; 7857; -.
DR Ensembl; ENST00000305409.3; ENSP00000304133.2; ENSG00000171951.5.
DR GeneID; 7857; -.
DR KEGG; hsa:7857; -.
DR MANE-Select; ENST00000305409.3; ENSP00000304133.2; NM_003469.5; NP_003460.2.
DR UCSC; uc002vnm.4; human.
DR AGR; HGNC:10575; -.
DR CTD; 7857; -.
DR DisGeNET; 7857; -.
DR GeneCards; SCG2; -.
DR HGNC; HGNC:10575; SCG2.
DR HPA; ENSG00000171951; Group enriched (adrenal gland, brain, pituitary gland).
DR MIM; 118930; gene.
DR neXtProt; NX_P13521; -.
Query Match 100.0%; Score 3207; Length 617;
Best Local Similarity 100.0%;
Matches 617; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MAEAKTHWLGAALSLIPLIFLISGAEAASFQRNQLLQKEPDLRLENVQKFPSPEMIRALE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAEAKTHWLGAALSLIPLIFLISGAEAASFQRNQLLQKEPDLRLENVQKFPSPEMIRALE 60
Qy 61 YIENLRQQAHKEESSPDYNPYQGVSVPLQQKENGDESHLPERDSLSEEDWMRIILEALRQ
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YIENLRQQAHKEESSPDYNPYQGVSVPLQQKENGDESHLPERDSLSEEDWMRIILEALRQ
Qy 121 AENEPQSAPKENKPYALNSEKNFPMDMSDDYETQQWPERKLKHMQFPPMYEENSRDNPFK
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AENEPQSAPKENKPYALNSEKNFPMDMSDDYETQQWPERKLKHMQFPPMYEENSRDNPFK
Qy 181 RTNEIVEEQYTPQSLATLESVFQELGKLTGPNNQKRERMDEEQKLYTDDEDDIYKANNIA
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 RTNEIVEEQYTPQSLATLESVFQELGKLTGPNNQKRERMDEEQKLYTDDEDDIYKANNIA
Qy 241 YEDVVGGEDWNPVEEKIESQTQEEVRDSKENIEKNEQINDEMKRSGQLGIQEEDLRKESK
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 YEDVVGGEDWNPVEEKIESQTQEEVRDSKENIEKNEQINDEMKRSGQLGIQEEDLRKESK
Qy 301 DQLSDDVSKVIAYLKRLVNAAGSGRLQNGQNGERATRLFEKPLDSQSIYQLIEISRNLQI
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 DQLSDDVSKVIAYLKRLVNAAGSGRLQNGQNGERATRLFEKPLDSQSIYQLIEISRNLQI
Qy 361 PPEDLIEMLKTGEKPNGSVEPERELDLPVDLDDISEADLDHPDLFQNRMLSKSGYPKTPG
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 PPEDLIEMLKTGEKPNGSVEPERELDLPVDLDDISEADLDHPDLFQNRMLSKSGYPKTPG
Qy 421 RAGTEALPDGLSVEDILNLLGMESAANQKTSYFPNPYNQEKVLPRLPYGAGRSRSNQLPK
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 RAGTEALPDGLSVEDILNLLGMESAANQKTSYFPNPYNQEKVLPRLPYGAGRSRSNQLPK
Qy 481 AAWIPHVENRQMAYENLNDKDQELGEYLARMLVKYPEIINSNQVKRVPGQGSSEDDLQEE
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 AAWIPHVENRQMAYENLNDKDQELGEYLARMLVKYPEIINSNQVKRVPGQGSSEDDLQEE
Qy 541 EQIEQAIKEHLNQGSSQETDKLAPVSKRFPVGPPKNDDTPNRQYWDEDLLMKVLEYLNQE
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 EQIEQAIKEHLNQGSSQETDKLAPVSKRFPVGPPKNDDTPNRQYWDEDLLMKVLEYLNQE
Qy 601 KAEKGREHIAKRAMENM 617
|||||||||||||||||
Db 601 KAEKGREHIAKRAMENM 617
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 2, 7-11, 13, 14, 23, 89, and 91 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Steward et al. WO 2008/008805 published January 17, 2008.
For present claims 1, 2, 7-11, 13, 14, 23, 89, and 91, Steward et al. teach SEQ ID NO: 87 (100% identity and the same length as present SEQ ID NO: 5), EM66, and manserin, and saline (i.e. pharmaceutically acceptable carrier), BSA (i.e. pharmaceutically acceptable carrier), and fusion polypeptides (please refer to the entire specification particularly paragraphs 218, 277, 286, 337, 345, 356, 362, 363, 379, 451; claim 46 in the specification).
Therefore, the teachings of Steward et al. anticipate the presently claimed pharmaceutical composition.
Claims 1, 2, 7-11, 13, 14, 23, 89, and 90 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. U.S. Patent Application Publication 2007/0116677 published May 24, 2007.
For present claims 1, 2, 7-11, 13, 14, 23, 89, and 90, Li et al. teach SEQ ID NO: 1 (100% identity and the same length as present SEQ ID NO: 5), carriers, PBS, and fusion polypeptides (please refer to the entire specification particularly the abstract; paragraphs 2, 3, 5-8, 10-14, 19, 21, 66). Li et al. also teach BSA, however, BSA is not in a formulation with the peptide (please refer to the entire specification particularly paragraphs 26).
Therefore, the teachings of Li et al. anticipate the presently claimed pharmaceutical composition.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 2, 7-11, 13, 14, 23, and 89-93 are rejected under 35 U.S.C. 103 as being unpatentable over Steward et al. WO 2008/008805 published January 17, 2008; Toneff et al., 2013, Beta-amyloid peptides undergo regulated co-secretion with neuropeptide and catecholamine neurotransmitters, Peptides, 46: 21 pages; and Jones et al., 2007, Blood-Brain Barrier Transport of Therapeutics via Receptor-Mediation, Pharm Res, 24(9): 1759-1771.
For present claims 1, 2, 7-11, 13, 14, 23, and 89-93, Steward et al. teach SEQ ID NO: 87 (100% identity and the same length as present SEQ ID NO: 5), EM66, and manserin, and saline (i.e. pharmaceutically acceptable carrier), BSA (i.e. pharmaceutically acceptable carrier), and fusion polypeptides (please refer to the entire specification particularly paragraphs 218, 277, 286, 337, 345, 356, 362, 363, 379, 451; claim 46 in the specification).
However, Steward et al. do not teach PBS.
For present claims 1, 2, 7, and 89-91, Jones et al. teach peptides in a PBS-BSA solution (please refer to the entire reference particularly section 2.2).
However, Steward et al. do not teach CRM197.
For present claims 1, 2, 7, 92, and 93, Jones et al. teach methods of making peptide-CRM197 fusion polypeptides to cross the BBB (please refer to the entire specification particularly section IV Diphtheria toxin receptor/Heparin binding epidermal growth-factor-like growth factor – page 9).
All the claimed elements (i.e. PBS, CRM197 fusion polypeptides) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective function (i.e. PBS solution comprising a polypeptide; CRM197 fusion polypeptides can cross the BBB) and the combination would have yielded predictable results (i.e. polypeptide in a PBS solution; CRM197 fusion polypeptides can cross the BBB) to one of ordinary skill in the art before the effective filing date of the claimed invention. The claims would have been obvious because the substitution of one known element (i.e. saline; genus of fusion polypeptide) for another (i.e. PBS; CRM197 fusion polypeptide) would have yielded predictable results (i.e. peptide in a PBS solution; CRM197 fusion to cross the BBB) to one of ordinary skill in the art before the effective filing date of the claimed invention. The claims would have been obvious because a particular known technique (i.e. making peptide, PBS, and BSA solution; utilizing CRM197 peptide fusions to cross the BBB) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Claims 1, 2, 7-11, 13, 14, 23, and 89-93 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. U.S. Patent Application Publication 2007/0116677 published May 24, 2007; Toneff et al., 2013, Beta-amyloid peptides undergo regulated co-secretion with neuropeptide and catecholamine neurotransmitters, Peptides, 46: 21 pages; and Jones et al., 2007, Blood-Brain Barrier Transport of Therapeutics via Receptor-Mediation, Pharm Res, 24(9): 1759-1771.
For present claims 1, 2, 7-11, 13, 14, 23, 89, and 90, Li et al. teach SEQ ID NO: 1 (100% identity and the same length as present SEQ ID NO: 5), carriers, PBS, and fusion polypeptides (please refer to the entire specification particularly the abstract; paragraphs 2, 3, 5-8, 10-14, 19, 21, 66). Li et al. also teach BSA, however, BSA is not in a formulation with the peptide (please refer to the entire specification particularly paragraphs 26).
However, Li et al. do not teach BSA in combination with a peptide.
For present claims 1, 2, 7, and 89-91, Jones et al. teach peptides in a PBS-BSA solution (please refer to the entire reference particularly section 2.2).
However, Li et al. do not teach CRM197.
For present claims 1, 2, 7, 92, and 93, Jones et al. teach methods of making peptide-CRM197 fusion polypeptides to cross the BBB (please refer to the entire specification particularly section IV Diphtheria toxin receptor/Heparin binding epidermal growth-factor-like growth factor – page 9).
All the claimed elements (i.e. BSA, CRM197 fusion polypeptides) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective function (i.e. BSA-PBS solution comprising a polypeptide; CRM197 fusion polypeptides can cross the BBB) and the combination would have yielded predictable results (i.e. polypeptide in a BSA-PBS solution; CRM197 fusion polypeptides can cross the BBB) to one of ordinary skill in the art before the effective filing date of the claimed invention. The claims would have been obvious because the substitution of one known element (i.e. PBS solution; genus of fusion polypeptide) for another (i.e. BSA-PBS solution; CRM197 fusion polypeptide) would have yielded predictable results (i.e. peptide in a PBS solution; CRM197 fusion to cross the BBB) to one of ordinary skill in the art before the effective filing date of the claimed invention. The claims would have been obvious because a particular known technique (i.e. making peptide, PBS, and BSA solution; utilizing CRM197 peptide fusions to cross the BBB) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
WO 2008/020192
U.S. Patent Application Publication 2019/0314375
Prathipati et al., 2016, Development of novel HDL-mimicking a-tocopherol-coated nanoparticles to encapsulate nerve growth factor and evaluation of biodistribution, Eur J Pharm Biopharm, 108: 126-135.
Pillai et al., 1995, Immunogenicity of Genetically Engineered Glutathione S-Transferase Fusion Proteins Containing a T-Cell Epitope from Diphtheria Toxin, Infection and Immunity, 63(4): 1535-1540.
Future Communications
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/AMBER D STEELE/Primary Examiner, Art Unit 1658